Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells

Anticancer Res. 2006 May-Jun;26(3A):1965-71.

Abstract

The role of Ca2+ on the effects of capsaicin on human leukemia HL-60 cells in vitro and the molecular mechanisms of capsaicin-induced apoptosis were investigated. The flow cytometric analysis indicated that capsaicin decreased the percentage of viable HL-60 cells, via the induction of G0/G1-phase cell cycle arrest and apoptosis. Capsaicin-induced G0/G1-phase arrest involved the suppression of CDK2 and the cyclin E complex, which are check-point enzymes for cells moving from G0/G1- to S-phase. Capsaicin-induced apoptosis was associated with the elevation of intracellular reactive oxygen species and Ca2+ production, decreased the levels of mitochondrial membrane potential, promoted cytochrome c release and increased the activation of caspase-3. An intracellular Ca2+ chelator (BAPTA) significantly inhibited capsaicin-induced apoptosis. Capsaicin-induced apoptosis was time-and dose-dependent. These results suggest that the capsaicin-induced apoptosis of HL-60 cells may result from the activation of caspase-3 and the intracellular Ca2+ release pathway.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • CDC2 Protein Kinase / biosynthesis
  • Calcium / metabolism*
  • Capsicum*
  • Caspase 3
  • Caspases / metabolism*
  • Cyclin D3
  • Cyclin E / antagonists & inhibitors
  • Cyclin E / biosynthesis
  • Cyclin-Dependent Kinase 2 / biosynthesis
  • Cyclins / biosynthesis
  • Cytochromes c / biosynthesis
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enzyme Activation
  • G1 Phase / drug effects
  • G1 Phase / physiology
  • HL-60 Cells
  • Humans
  • Membrane Potentials / drug effects
  • Mitochondrial Membranes / physiology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reactive Oxygen Species / metabolism
  • Resting Phase, Cell Cycle / drug effects
  • Resting Phase, Cell Cycle / physiology
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / metabolism*

Substances

  • BAX protein, human
  • CCND3 protein, human
  • Cyclin D3
  • Cyclin E
  • Cyclins
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Egtazic Acid
  • Cytochromes c
  • CDC2 Protein Kinase
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium